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Redox Report

Redox Report

IF: 5.2
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Characterization of naphthoquinones as inhibitors of glutathione reductase and inducers of intracellular oxidative stress

Published:1 December 2024 DOI: 10.1080/13510002.2024.2432830 PMID: 39620933
Xiaowan Chen,?Yan Ma,?Ziming Yang,?Dingjie Shen,?Xia Li,?Maowei Ni,?Xiaoling Xu,?Wei Chen

Abstract

Glutathione reductase (GR), one of the most important antioxidant enzymes in maintaining intracellular redox homeostasis, has become a novel target to suppress cancer cell growth and metastasis. In this work, we evaluated a series of naphthoquinones (NQs) as potential GR inhibitors and elucidated the mechanism of inhibition. NQ-6, one of the most potent compounds among this series, inhibited GR in vitro and in vivo and was identified as a competitive and irreversible inhibitor. The Ki and kinact values of NQ-6 were determined to be 17.30?±?3.63?μM and 0.0136?±?0.0005?min-1, respectively. The tandem mass spectrometric analysis revealed that the two substrate binding sites Cys61 and Cys66 of yeast GR were modified simultaneously through arylation or only Cys66 was covalently modified by NQ-6. Intracellular reactive oxygen species, collapsing of mitochondrial membrane potential and protein S-glutathionylation elevation were induced by NQ-6. NQs can be valuable compounds in GR inhibition and oxidative stress-related research.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Acetonitrile 75-05-8 C2H3N 1022 suppliers $61180.00
Bovine albumin 9048-46-8 N/A 498 suppliers $15.00-$17060.00
Trypsin 9002-07-7 C35H47N7O10 453 suppliers $17.70-$24930.00
FETUIN 9014-81-7 NULL 66 suppliers $37.07-$4380.00

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